The invention relates to a process for the production of human cartilage implants from, e.g., chondrocytes cultivated in vitro.
Articular cartilage suffers from a very limited ability for repair of joint surface damage. A workable concept for surgical therapy of joint surface damage based on cartilage produced in vitro has the prerequisite, inter alia, that cartilage implants can be obtained from autologous cells (chondrocytes or mesenchymal stem cells), which come as close as possible to the original with respect to their biochemical composition and biomechanical properties. In principle, both chondrocytes and mesenchymal stem cells are suitable for this purpose.
Since autologous cells are only available in small number in the form of a biopsy, there is a necessity for effective in vitro expansion. This is a particular challenge, since, as is known from the literature, a loss of the differentiated phenotype which increases with the number of passages is observed. This means that while the synthesis of cartilage can be promoted merely by increasing cell/cell contact on use of primary cells or of first-passage cells, this method fails if cells have to be passaged more frequently for the purposes of multiplication. Neither has it hitherto been achieved in human cells to halt the decrease in the chondrogenesis potential during the multiplication phase by means of various additives, such as certain sera or certain growth factors, such as bFGF.
It is already known to multiply human cartilage cells in a cell culture vessel, e.g., a dish/bottle, (cells de-differentiate in this monolayer cultivation) with subsequent re-differentiation of the cells in alginate gel. The cells and their surrounding matrix are subsequently analyzed using different methods within the alginate or after dissolution of the cells out of the alginate (Bonaventure J. et al., Exp. Cell Res. 212 (1):97-104 (1994), Reexpression of Cartilage-Specific Genes by Dedifferentiated Human Articular Chondrocytes Cultures in Alginate; Yaeger P. C. et al. Exp. Cell Res. 237:318-325 (1997), Synergistic Action of Transforming Growth Factor-xcex2 and Insulin-like Growth Factor-I Induces Expression of Type II Collagen and Aggrecan Genes in Adult Human Articular Chondrocytes).
An object of the present invention is to provide a process for the cultivation of a substantially differentiated cartilage tissue (not individual cells) of sufficient size (e.g., having a diameter or side dimensions of about 0.1-5 cm, preferably about 0.2 to 3 cm) which avoids the above-mentioned disadvantages from the prior art, so that the cartilage tissue can be implanted in a xe2x80x9cpress-fitxe2x80x9d manner (i.e. with rotationally stable seating) in joint cartilage defects.
Upon further study of the specification and appended claims, further objects and advantages of this invention will become apparent to those skilled in the art.